Jul 16, 2019
A reconstituted mammalian mRNA transport system selectively transports defined amounts of axonal mRNAs
Date: July 16, 2019 |
2:00 pm –
Speaker: Sebastian Maurer, Centre for Genomic Regulation
Location: Mondi Seminar Room 2, Central Building
Using biochemical in vitro reconstitutions in combination with fast, single-molecule sensitivity fluorescent imaging we show that the tumor suppressor adenomatous polyposis coli (APC) functions as adaptor linking the axonally localized beta-actin and beta-tubulin mRNAs to the heterotrimeric kinesin-2 KIF3A/B/KAP3. We demonstrate that the kinesin-2 cargo-adaptor KAP3 is required to couple APC-RNA complexes to the motor protein, while APC activates transport by recruiting the kinesin to microtubules. Remarkably, our minimal in vitro system shows that two proteins are sufficient for processive mRNA transport and also to generate key-characteristics of neuronal mRNA transport as mRNA-cargo specificity and transport of defined numbers of mRNAs. We further demonstrate that guanine-rich sequences increase mRNA transport efficiency and balance the access of different mRNAs to the transport system to compensate for relative mRNA abundance. Our results reveal for the first time a minimal set of proteins sufficient to drive kinesin-based, mammalian mRNA transport.